Albumin-Bilirubin Grade as a Novel Predictor of Survival in Advanced Extrahepatic Cholangiocarcinoma

Aim. Child-Pugh (CP) grade has been used to assess liver function and postoperative outcomes in biliary tract neoplasms. The aim of this study was to preliminarily explore the prognostic significance of an alternative model of liver function, called albumin-bilirubin (ALBI) grade, in patients with extrahepatic cholangiocarcinoma (EHC). Methods. A total of 109 advanced EHC patients, who received percutaneous transhepatic biliary stenting combined with iodine-125 seed implantation from January 2012 to April 2017 in our department, were enrolled. Preoperative clinical data were collected to calculate the CP and ALBI grades. The performance of ALBI score in predicting postoperative death was compared with that of CP score by using the receiver operating characteristic (ROC) curve. Kaplan-Meier analysis and Cox regression model were performed for overall survival (OS) analysis. Results. The median survival time of our cohort was 12 months, and the 1-year and 2-year survival rates were 56.9% and 12.8%, respectively. The area under the ROC curve of ALBI score for predicting death was significantly greater than the CP score (0.751, 95% CI: 0.641–0.861, P<0.001 vs. 0.688, 95% CI: 0.567–0.809, P<0.001). The univariate analysis revealed that the factors related to overall survival of EHC were carbohydrate antigen 19-9, total bilirubin, albumin, ALBI grade, and CP score. In multivariate analysis, ALBI grade (HR = 1.65, 95% CI: 1.04–2.61, P=0.032), but not CP score, was identified as an independent prognostic model. Conclusion. We demonstrated that the ALBI grade could be used as a predictor of survival in unresectable EHC patients.

Correlation between overall survival and other efficacy endpoints in advanced biliary tract cancer: Literature-based analysis from 13 randomized trials of first-line chemotherapy.

352 Background: Chemotherapy for advanced biliary tract cancer (ABC) has progressed. Now gemcitabine plus cisplatin combination is considered the standard 1st-line treatment based on the results of many randomized studies. However, the impact of various efficacy parameters on overall survival (OS) remains unclear. Methods: We searched PubMed database with the key words of (“biliary tract neoplasms” or “bile duct neoplasms” or “gallbladder neoplasms” or “cholangiocarcinoma” [All fields]) AND (“chemotherapy”[All fields]) AND Clinical trial [ptyp] between Apr 1984 to Jun 2013 and abstracts presented at the meetings of ASCO/Gastrointestinal Cancers Symposium (2004–2013) and ESMO/WCGC (2002–2013). Then we identified randomized trials of 1st-line chemotherapy for ABC, and analyzed the relations between the results of OS and those of progression-free survival (PFS) or time to progression (TTP), response rate (RR), disease control rate (DCR), post-progression survival (PPS = median OS − median PFS/TTP), and the proportion of patients who received 2nd-line chemotherapy (%2nd). Results: Among 329 papers/abstracts retrieved, 13 randomized trials, 26 treatment arms of first-line chemotherapy for ABC were identified. Number of trials with information on median OS, median PFS/TTP, hazard ratio (HR) for OS and PFS/TTP, RR, DCR, and %2nd were 13, 13, 6, 13, 12, and 7, respectively. The analysis of all these trials demonstrated the median values (range) of OS, PFS/TTP, HR of OS, HR of PFS/TTP, RR, DCR, PPS, and %2nd were 9.4 (4.6–13) months, 5.3 (2.7–8.5) months, 0.71 (0.39–0.93), 0.65 (0.44–0.85), 20 (7.1–36) %, 67 (21–87) %, 4.0 (1.0–7.6) months, and 41 (15–79) %, respectively. Spearman rank correlation coefficient of differences (Δ) OS with ΔPFS/TTP, ΔRR, ΔDCR, and ΔPPS were 0.66, − 0.07, 0.66, and 0.34, respectively. The correlation coefficient between HRs for PFS/TTP and OS was 0.60. The correlation coefficient between ΔPPS and Δ%2nd was − 0.15. Conclusions: OS was moderately associated with PFS/TTP and DCR.

Chemotherapy in advanced biliary tract carcinoma (BTC): A comprehensive analysis

14036 Background: BTC are uncommon but highly fatal malignancies in the United States and Europe. Unfortunately, most BTC are diagnosed at advanced stages when the tumor is unresectable. Due to the lack of phase III studies there is no standard regimen for palliative chemotherapy of BTC. The aim of this study was to analyze existing data of published clinical trials, even small and non-randomized, and identify superior regimens, which may represent a quasi standard of care of palliative chemotherapy in this disease. Methods: Data for this analysis were identified by searches of PubMed and references from relevant articles using the search terms “biliary tract neoplasms”, “bile duct neoplasms”, “cholangiocarcinoma”, and “gallbladder neoplasms”. Only papers published in English since 1985 were included. Additionally abstracts from ASCO meetings presented since 1999 were included. Results: 88 trials were analyzed. The overall response rates (OR) of this trials were in the range of 0–83%. There were 497 responders out of 2137 patients corresponding to a pooled OR of 23.3% (95%CI 21.5–25.2%). The median progression free survival (PFS) and overall survival (OS) for all patients was 4.1 and 8.0 months, respectively. There was a significant correlation between OR and PFS (r=0.49; p=0.001) and PFS and OS (r=0.76; p=0.000) but not between OR and OS. Gemcitabine (GEM) and platinum analogs (P) had a significant positive impact on OR, whereas the impact of taxanes and irinotecan was negative. OR of subgroups defined by 5-FU, GEM, and P were analyzed in detail. There was only a trend of an increased OR between 5-FU and GEM without P (17 vs 22%). Combination with P increased significantly the OR of 5-FU by 10% (17 vs 27%) and of GEM by 20% (22 vs 42%). Conclusions: The pooled OR of mostly small trials of palliative chemotherapy in BTC is about 23%. With GEM alone no significant improvement could be achieved compared to 5-FU or capecitabine. However, doublets of GEM in combination with P synergistically increased OR. Results of GEM plus P are promising and should be further evaluated by large RCT. In the meantime GEM plus P may represent at least a good option for patients in good general condition. No significant financial relationships to disclose.